Inhibitors of protein kinase C block activation of B lymphocytes by bacterial lipopolysaccharide

Activation of murine splenic B lymphocytes (B cells) by bacterial lipopolysaccharide (LPS) was found to be markedly inhibited by 1-(5-iso-quinolinylsulfonyl)-2-methylpiperazine (H-7) and N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide (H-8), two potent inhibitors of protein kinases. The higher sensitivity of DNA synthesis, RNA synthesis and protein N-glycosylation activity to H-7, relative to H-8, strongly supports the proposal that protein kinase C plays a critical role in the activation of B cells. A kinetic study on the time of addition of H-7 indicated that protein kinase C promoted the activation process continuously after the addition of LPS.